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(Circulation. 1999;100:2113-2118.)
© 1999 American Heart Association, Inc.
Basic Science Reports |
Progressive Loss of Myocardial ATP Due to a Loss of Total Purines During the Development of Heart Failure in Dogs
A Compensatory Role for the Parallel Loss of Creatine
From the NMR Laboratory for Physiological Chemistry, Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass (W.S., J.S.I.); the Cardiovascular and Pulmonary Research Institute, Allegheny University of Health Sciences, Pittsburgh, Pa (W.S., M.A.M., R.P.S.); and Weis Center for Research, Penn State University, College of Medicine, Hershey, Pa (K.A., M.U., S.F.V.).
Correspondence to Weiqun Shen, MD, PhD, 221 Longwood Ave, Room 247, Boston, MA 02115.
Background—Whether myocardial ATP content falls in heart failure is a long-standing and controversial issue. The mechanism(s) to explain any decrease in ATP content during heart failure have not been identified.
Methods and Results—Cardiac dysfunction, heart failure, and a
prolonged steady state of heart failure were induced by chronic right
ventricular pacing for 1 to 2 weeks, 3 to 4 weeks, and 7 to
9 weeks in dogs. Cardiac function and myocardial O2
consumption (M
O2) were measured with the
dogs in the conscious state. ATP, total purine, and creatine were
measured in biopsy specimens obtained at each stage. ATP and the total
purine pool progressively fell at rates of 0.12 and 0.15 nmol ·
mg protein-1 · d-1, despite an
increase in MO2. The rate of loss of
creatine was 1.06 nmol · mg protein-1 ·
d-1, 7 times faster than the depletion of total
purine.
Conclusions—(1) ATP contents progressively decreased during heart failure as a result of a loss of the total purine pool. The loss of purines may be due to inhibition of de novo purine synthesis. (2) Loss of creatine is an early marker of heart failure and may serve as a compensatory mechanism minimizing the reduction of the total purine pool in the failing heart.
Key Words: adenosine triphosphate • purine • creatine • oxygen • heart failure
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